Abstract

A high-performance liquid chromatographic method is presented for the determination of trimethoprim (TMP), 3'-hydroxy-TMP, 4'-hydroxy-TMP, α-hydroxy-TMP and two TMP N-oxides. The last two metabolites appear to decompose on liquid extraction. TMP and its oxidative metabolites are separated using a C 18 radial-compression column and quantified by UV detection at 230 nm. Calibration curves are linear from 0.5 to at least 50 μ M. The limit of detection is 0.05–0.15 μg/ml. In in vitro rat liver metabolism studies, 3'- and 4'-hydroxylation of TMP appear to be important metabolic pathways whereas TMP N-oxides are minor metabolites.

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